Association of autistic spectrum disorder and the measles, mumps, and rubella vaccine: a systematic review of current epidemiological evidence

Wilson K, Mills E, Ross C, McGowan J, Jadad A

CRD summary

This review assessed the association between autistic spectrum disorder (ASD) and the measles, mumps and rubella (MMR) vaccine. The authors found no association between ASD and MMR, but there was insufficient evidence to completely exclude a possible association between MMR and a rare variant form of ASD. This was a well-conducted review, but the quality and nature of the included studies were varied.

Authors' objectives

To review evidence for and against the existence of an association between autistic spectrum disorder (ASD) and the measles, mumps and rubella (MMR) vaccine.

Searching

CINAHL (from 1982), PsycINFO (from 1872), MEDLINE (from 1966), PREMEDLINE, TOXLINE (from 1966), Biological Abstracts (from 1990), EMBASE (from 1982) and HealthSTAR (from 1975) were searched up to January or February 2003. The Cochrane Library (Issue 4, 2002) was also searched. The search terms were reported and language restrictions were not imposed. The bibliographies of reviews were also checked and authors of published studies were contacted for further relevant studies.

Specific interventions included in the review

Studies of MMR vaccination were eligible for the review.

Participants included in the review

The participants in any study that investigated the possible association between ASD and MMR vaccination and which described the methods for the diagnosis of ASD were eligible for the review. The studies had to have reported a systematic method of identifying a sample. All of the included studies were of children: those diagnosed with ASD or with some developmental delay disorder (with possible temporal association with MMR); those who had developed possibly significant symptoms after MMR vaccination; those who had all received the MMR vaccine; or inclusive or random samples of a general population of children. Two studies included a control group: one of matched controls, and one comprising a clinical sample from before the introduction of the MMR vaccine. Overall, the included studies were based on nine distinct sources of data.

Outcomes assessed in the review

Studies that reported outcomes relevant to the testing of the association between the development of ASD and MMR vaccination were eligible for the review. The studies had to describe methods used for the diagnosis of ASD. The included studies compared rates of ASD in children vaccinated with MMR and unvaccinated children; examined the change in rates of ASD associated with change in MMR vaccination coverage; and examined the temporal association between ASD or a variant of ASD and MMR. The included studies defined variant ASD as developmental regression or gastrointestinal symptoms.

How were decisions on the relevance of primary studies made?

The authors stated that they selected papers for the review independently and in duplicate. Any disagreements were resolved by consensus, with the help of a third reviewer if required.

Assessment of study quality

The authors did not report a method for formally assessing study validity. Some aspects of validity were considered in the paper: study power, adjustment for potential confounders and limitations of the study design.

Data extraction

The data were extracted in duplicate and any disagreements were resolved by discussion and consensus.

Methods of synthesis

How were the studies combined?

The study findings were combined in a narrative. Four hypotheses (see Results) were examined.

How were differences between studies investigated?

The studies were not formally tested. Details of the studies were presented and compared in the tables and the text.

Results of the review

Twelve studies were included in the review. The total number of participants was unclear. The size of the studies varied enormously: where reported, the sample size ranged from 31 children to 1.8 million vaccinations.

Hypothesis 1: ASD rates are higher in those who receive the MMR (one study, number of participants unclear). Both adjusted and unadjusted analyses found no statistically significant difference in autism or ASD between children vaccinated with MMR and those not vaccinated.

Hypothesis 2: MMR vaccination implementation has resulted in increasing rates of ASD (6 studies). No statistically significant association was found in any of the studies.

Hypothesis 3: the development of ASD is temporally associated with the MMR vaccine (8 studies). Three studies examined the age at which ASD was diagnosed and six looked for an increase in the rate of ASD. No study found an association. Hypothesis 4: a new variant form of ASD is associated with the MMR vaccine (4 studies). No study found an association with bowel symptoms and MMR vaccination and ASD.

Authors' conclusions

The current literature does not suggest an association between developing ASD and the MMR vaccine. There was insufficient epidemiological study data to completely dismiss the possibility of an association between MMR vaccination and a rare variant form of ASD.

CRD commentary

The aims of the review were clear, although because of the review's objective the inclusion criteria for the participants and outcomes were necessarily general. The literature search was thorough and included contact with experts; it does not seem likely that important studies were missed. Some of the review methods were reported and it appeared that reasonable steps were taken to minimise reviewer bias and error. Details of the primary studies and summarised results were presented in the review, and the use of a narrative synthesis was appropriate. However, the synthesis was brief and the varied quality and nature of the included studies was not discussed in detail; some important issues for discussion might have been missed. Overall, the results of all the primary studies support the authors' conclusions.

Implications of the review for practice and research

Practice: The authors stated that given that there are real risks associated with not vaccinating with MMR, but only theoretical risks of ASD, then the current policy of vaccination with MMR should continue.

Research: The authors stated that any further research should attempt to determine whether there is an association between the MMR vaccine and specific phenotypes of ASD.

This additional published commentary may also be of interest. Jack S. Review: existing epidemiological evidence does not show an association between mumps, measles, and rubella vaccination and autism. Evid Based Nurs 2004;7:25.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.